ASPSCR1 (ASPSCR1 tether for SLC2A4, UBX domain containing) functions as a tethering protein that regulates glucose homeostasis by sequestering GLUT4-containing vesicles in the cytoplasm in the absence of insulin [UniProt]. The protein also plays a crucial role in organizing the early secretory pathway, specifically localizing to the ER-Golgi Intermediate Compartment (ERGIC) where it forms biomolecular condensates and stabilizes ERGIC membranes to support diverse secretory and degradative trafficking pathways 1. ASPSCR1 contains a central disordered region that mediates membrane recruitment and an N-terminal region for oligomerization 1. Clinically, ASPSCR1 is most significant as part of the ASPSCR1::TFE3 fusion oncoprotein, which serves as the primary genetic driver of alveolar soft part sarcoma (ASPS) and certain renal cell carcinomas 2. This fusion protein reprograms transcription by organizing enhancer loops around hexameric VCP/p97, driving core programs involved in cell proliferation, angiogenesis, and mitochondrial biology 3. Patients with ASPSCR1-TFE3 fusion cancers show better response to immune checkpoint inhibitor-based combination therapy compared to other TFE3 fusion variants 4, making fusion partner identification clinically relevant for treatment decisions.